This invention provides a system for the extrapolation of an actual glucose concentration in order to determine future glucose concentrations. Another configuration of the system uses extrapolated glucose concentrations to determine the proper dose of insulin to administer to a patient.
Diabetes mellitus is a group of chronic metabolic disorders characterized by raised blood glucose levels and impaired carbohydrate, fat, and protein metabolism. The insulin deficiency responsible for this disorder results from a defect in insulin secretion or the effect of insulin on the organism. Absolute insulin deficiency—which occurs in type I diabetes—is usually caused by an auto-immunological destruction of insulin-producing beta cells in the pancreas. These patients must rely on exogenous sources of insulin. Individuals with type II diabetes are resistant to insulin and suffer from impaired insulin secretion. Both of these disorders can occur to varying degrees. The exact causes of this disease are not known. Treatment of relative insulin deficiency ranges from dietary modifications and oral anti-diabetics to exogenous insulin administration.
Patients who suffer from Diabetes mellitus over the long term and, therefore, have chronic hyperglycemia, develop organ damage, impairment, and even failure. The eyes, kidneys, nerves, blood vessels, and the heart are affected in particular. Prevention of these late complications is the main goal of diabetes therapy. In the most commonly used therapy today, patients are administered slow-acting insulin that covers the basal insulin demand. They are also administered a bolus of normal insulin or a fast-acting insulin to offset the carbohydrates consumed during a meal.
This invention concerns the extrapolation of measured glucose concentrations to determine future concentrations in order to provide the patient with the basis for determining proper insulin dosage, or to properly control an insulin infusion pump.
A biostator is known in the prior art that is used to perform glucose measurements in venous blood and administer computer-controlled intravenous insulin and glucose infusions based on these measurements. A serious disadvantage of the biostator, however, is that intravenous infusions must be carried out to achieve proper regulation, and these infusions basically must be performed under stationary conditions. The patient cannot perform the infusion himself due to the high risk of infection.
The goal of development work, therefore, must be to maintain patients within a normal range of glucose concentration by means of subcutaneous insulin infusions that can be carried out by the patient himself or by means of implanted pumps. Due to the delayed effect of subcutaneously administered insulin, however, is it much more difficult to find a control procedure with which the goal can be achieved. U.S. Pat. No. 5,822,715 describes a diabetes management system with which an insulin dose to be injected by the patient is determined based on measured blood glucose values and previously administered insulin doses. To calculate the insulin dose to be administered, a future blood glucose value is calculated for this patient, and its deviation from a target blood glucose value is determined. This procedure only takes into consideration the administered insulin doses and their effectiveness profile, however. Other influences on blood glucose concentration are not explicitly taken into consideration. Our studies show that consideration of administered insulin quantities alone is not sufficient to keep glucose concentration within a normal range. It was found in particular that cases of strong hyperglycemia occur in regulating procedures based solely on this technique.
The object of the present invention was to propose a system for the reliable extrapolation of a glucose concentration and the determination of insulin doses to be administered subcutaneously. It was found with the invention that it is particularly important to take consumed carbohydrates into account when developing a regulating system that achieves the goal of subcutaneous insulin infusion. Accordingly, this invention provides a system for the extrapolation of glucose concentrations, comprising                a data input device (EI) for entering the insulin doses (Ii) administered to the patient and their times of administration (ti),        data input device (EK) for entering the carbohydrates (KHj) consumed or to be consumed by the patient, and the time they are consumed (tj),        a unit (GM) for determining the actual glucose concentration (Ga) in a patient's bodily fluid at a specific point in time (ta),        a memory unit (M) for storing the insulin doses administered and their times of administration, and the carbohydrates consumed and the times they were consumed,        an evaluation device for evaluating the data stored in the memory unit and for extrapolating a glucose concentration at a point in time (tp) that is later than the time of measurement (ta), and whereby the extrapolation comprises the following steps:        determination of the portion (Iwirk) of insulin doses that take effect within the interval between measurement and the projected moment,        determination of the portion (KHwirk) of carbohydrates consumed that take effect within the interval between measurement and the projected moment,        determination of an extrapolated glucose concentration (Gp) with consideration for the effective insulin doses (Iwirk) and the effective carbohydrate intake (KHIwirk).        
A system according to the invention comprises a data input device (EI) for entering administered insulin doses and their times of administration. This data input device can be a keyboard, for instance, by means of which the patient himself enters the insulin dose that he administered or had administered. The time of administration can be entered manually as well. The data input device could also be combined with a clock so the patient has the option of selecting time of input as the time of administration. It is also possible to combine a device that performs the administration, e.g., an automatic insulin pump, with a transmission device that transmits the administered insulin dose and its time of administration to the data input device. This transmission can take place over a fixed wire or via telemetric connection. It is also possible that the patient operates an infusion device himself, such as an insulin pump outfitted with a transmission unit that transmits the administered insulin dose along with the time of administration to the data input device.
The system also comprises a unit (GM) that determines a glucose concentration at a specific point in time. Blood glucose meters are known in the prior art with which glucose concentration can be measured in a capillary blood sample collected by the patient from the fingertip and then applied to a test element, for instance. These devices will not be described in further detail because they have been known for some time. To determine blood glucose values, it is also possible to implant measurement sensors in the body (e.g., intravasal, interstitial). This technology has not become popular because the sensors tend to drift. Another possibility for the determination of glucose values is based on measurements in interstitial fluid. Devices are known, for instance, with which small quantities of interstitial fluid can be collected through thin cannula and then analyzed. To perform subcutaneous measurements it is also possible to implant miniaturized catheters with which microdialysis or ultrafiltration can be performed, so that measured results can be provided at close intervals. A device based on microdialysis is described in U.S. Pat. No. 5,174,291, for instance. A device based on the principle of ultrafiltration is described in U.S. Pat. No. 4,777,953. These devices will not be discussed in further detail here.
The carbohydrates consumed by the patient and their time of consumption are recorded by a second data input device (EK). However, data input devices for insulin doses and carbohydrates can be provided by the same physical device, e.g. a keyboard, for entering both, administered insulin doses as well as consumed carbohydrates. Currently, diabetics typically estimate their insulin demand themselves based on the quantity of carbohydrates they consumed or are planning to consume, and then inject themselves with the calculated insulin dose before or directly after eating. The diabetic determines carbohydrate units by calculating the number of bread exchanges using tables for different types of food. According to the invention, the diabetic, nurse, or another caregiver enters the number of carbohydrate units or bread exchanges determined in the second data input device. This can be accomplished using a keyboard that is part of the system, for instance. Since the determination of carbohydrates consumed or to be consumed is relatively inaccurate by nature, one can use preprogrammed keys to enter a small, normal, or heavy meal, instead of a numerical entry. The system assigns 2, 4, or 6 carbohydrate units to these keys, for instance, which are used in the formula described below. It is also possible to provide selection keys or a selection field with which values in bread exchange increments of 0.5 can be entered. It is important that the times of carbohydrate consumption also be entered as accurately as possible. To ensure this, a clock can be provided in the data input device or the system that selects the time of input as the time of carbohydrate consumption and pairs it with the value of carbohydrate units consumed. The system should also provide an option for the user to change this time or to enter it himself directly if necessary.
The system also comprises a memory unit (M) for storage of administered insulin doses and their times of administration, as well as carbohydrate units consumed and their times of consumption, so they can be used as the basis for a subsequent evaluation. Such memory components—known as RAM—have been known for some time in the prior art.
An important component of the present system is an evaluation unit for the evaluation of data stored in the memory unit according to a predetermined evaluation procedure. As mentioned previously, the evaluation unit performs an extrapolation, by means of which a future glucose concentration (Gp) is determined. It was found that such an extrapolated glucose concentration is a suitable control variable for the determination of required insulin or glucose doses, and for the early detection of hypoglycemia or hyperglycemia. The extrapolation includes the determination of the portion of insulin dose that will become effective in the interval between measurement and the extrapolated point in time, and the determination of the portion of the carbohydrates consumed that takes effect in this time interval. In accordance with the invention it was found that these two parameters are the most important, and that taking them into account leads to an extrapolated glucose concentration that allows for a sufficiently exact determination of future glucose concentrations and required insulin doses. The effectiveness of the determination procedure based on this method will be demonstrated later using experimental data.
The portion (Iwirk) of insulin doses that become effective in the interval between the actual measurement (ta) and the extrapolated point in time (tp) can be determined by taking into account the kinetics of effectiveness of the insulin used.